Archive for category Pharmacological agents'

HAEMOSTATIC AGENTS enhance the process of haemostasis, which is the arrest of blood loss from damaged blood vessels, and is essential to life. It involves three key components and their processes: platelets, blood vessels (the vascular endothelium and smooth muscle of the wall), and the blood-borne coagulation cascade system. To an extent, these components can be separated, but proper formation of the haemostatic plug in vivo requires interaction of all. For instance, blood coagulation in vitro is rapid and efficiently forms a clot as such, but it is not the same entity as the thrombus of platelets enmeshed in fibrin that constitutes the functional haemostatic plug which is required in haemostasis to prevent haemorrhage. Similarly, in vivo, in a patient with a deficiency of platelets, there may be spontaneous bleeding giving a purple coloration in the skin (thrombocytopenic purpurea); though the clotting time of the blood is unchanged, the bleeding time is prolonged. The processes involved in formation of fibrin are described in more detail at ANTITHROMBINS and ANTICOAGULANTS. Briefly, some agents are direct-acting thrombin antagonists, binding avidly to this enzyme and thus preventing the key stage in blood coagulation Read more […]

GLUCOCORTICOIDS are members of the corticosteroid family, with actions similar to the steroid hormones secreted by the adrenal cortex. There are two main types of corticosteroids: glucocorticoids and MINERALOCORTICOIDS. Glucocorticoids that are important physiologically include hydrocortisone (cortisol), corticosterone and cortisone. These are essential for utilization of carbohydrate, fat and protein in the body, and in the normal response to stress. Naturally occurring and synthetic glucocorticoids have a powerful antiinflammatory effect. In contrast, the mineralocorticoids (e.g. aldosterone) are necessary for the regulation of the salt and water balance of the body. Corticosteroids can be used in hormone replacement therapy. For instance, the glucocorticoid hydrocortisone and the mineralocorticoid fludrocortisone can be given to patients for replacement therapy where there is a deficiency, or in Addison’s disease, or following adrenalectomy or hypopituitarism. The glucocorticoids are potent antiinflammatory and antiallergic agents, frequently used to treat inflammatory and/or allergic reactions of the skin, airways and elsewhere. Absorption of a high dose of corticosteroid over a period of time may also cause undesirable Read more […]

GASTRIC SECRETION INHIBITORS act at some stage in the control process to inhibit the enzymic or gastric acid secretions of the stomach, with the latter being a major therapeutic target. The neuronal, hormonal and paracrine control of gastric acid secretion from the parietal cells of the gastric mucosa is complex. The pathways involved include acetylcholine via the parasympathetic innervation of the stomach, the hormone gastrin. the paracrine agent histamine and possibly the paracrine hormone gastrin-releasing peptide. Anticholinergic agents have not proved very valuable in the long-run, having a limited ability to reduce acid secretion at doses that can be tolerated in view of widespread side-effects. Some more recently developed agents show gastric-selectivity (they are Mrcholinoceptor-preferring ligands, which may be the reason for their selectivity), e.g. pirenzepine and telenzepine: see muscarinic cholinoceptor antagonists. Gastrin receptor antagonists and gastrin-releasing peptide antagonists have now been developed for experimental use, but it is not yet clear if either will be useful clinically. See BOMBESIN RECEPTOR ANTAGONISTS; CHOLECYSTOKININ RECEPTOR ANTAGONISTS. Histamine H2-receptor antagonists Read more […]

FIBRINOLYTIC AGENTS help in the dissolution of thrombi or blood clots. Some agents used clinically are versions of endogenous agents, and others are agents foreign to the body, with a number of modes of action. Blood coagulation involves the conversion of fluid blood to a solid gel or a clot. The formation of a clot helps in the process of haemostasis (see HAEMOSTATICS). The formation of fibrin filament, together with the adhesion and activation of platelets, helps form the haemostatic plug, which serves to block the damaged blood vessel wall. The actual elements of the clot, insoluble strands of fibrin, are the end-product of a cascade largely involving serine protease enzymes, notably thrombin, and blood-borne proteins. A thrombus is the unwanted formation of a haemostatic plug in blood vessels, often within the veins or arteries of the heart, commonly in pathological conditions associated with arterial disease or where there is stasis. Pieces of the thrombus may break off and form an embolism, which may lodge in vessels in the lungs or brain causing damage to the tissues supplied. Thrombolytic drugs are able actually to dissolve thrombi. In contrast, neither antiplatelet drugs nor anticoagulants are necessarily Read more […]

ENZYMES can be used in therapeutics, though in general there are difficulties in delivering them to their proposed sites of action. There are commonly serious side-effects, normally immune reactions. There have been repeated attempts to use proteolytic enzymes in therapeutics to supplement deficiencies within the gastrointestinal tract, and necessarily there are difficulties in administering such enzymes without erosion of the mouth and upper digestive tract. Some notes follow on enzymes currently used. Anistreplase is a plasminogen streptokinase activator used as a fibrinolytic agent in the treatment of acute myocardial infarction. Crisantaspase (asparaginase) is an enzyme isolated from E. coli, which is thought to have some activity as an anticancer and antileukaemic agent. Batroxobin from snake venom is a serine protease and with its thrombin-like enzyme it is a haemostatic and defibrinogenating agent, and can be used in peripheral arterial circulatory disorders. Cellulase is a concentrate of cellulose-splitting (cellulytic) enzymes isolated from Aspergillus niger. It can be given by mouth, in combination with other digestive enzymes, to aid digestion. Chymopapain is a proteolytic enzyme isolated from Carica papaya, Read more […]

DOPAMINE RECEPTOR AGONISTS act to stimulate dopamine receptors, and these have a major neurotransmitter role in the CNS. Dopamine is also a precursor in the formation of the catecholamine monoamine neurotransmitter noradrenaline and the hormone adrenaline. The distribution of dopamine in the brain is very non-uniform. There is some in the limbic system, and a large proportion is found in the corpus striatum — a part of the extrapyramidal motor system which is concerned with the coordination of movement. Dopamine-containing nerves are found in three main pathways in the brain. The nigrostriatal pathway contains about 75% Of the dopamine in the brain, and the cell bodies lie in the substantia nigra and the nerves terminate in the corpus striatum. The second important pathway is the mesolimbic pathway, the cell bodies of which lie in the mid-brain and project to parts of the limbic system, particularly the nucleus accumbens. The third, the tubero-infundibular system, consists of short neurons that run from the arcuate nucleus of the hypothalamus to the median eminence and the pituitary gland, the secretions of which they regulate. With respect to disturbances of dopamineneurotransmitter function, the first-mentioned Read more […]

DIURETICS are used to reduce fluid in the body by increasing the excretion of electrolytes by the kidney — so increasing urine production. They have an extensive use. Reducing oedema is, in itself, of benefit in some disorders, and diuretics may be used in acute pulmonary oedema, congestive heart failure, some liver and kidney disease, glaucoma and in certain electrolyte disturbances, such as hypercalcaemia and hyperkalcaemia. The commonest use of diuretics is in antihypertensive therapy, where their action of reducing oedema is of value in reducing the load on the heart, which then — over some days or weeks — gives way to a beneficial reduction in blood pressure (that seems associated with vasodilator action). See ANTIHYPERTENSIVE AGENTS. In relation to their specific actions and uses, diuretics can be divided into a number of distinct classes. Osmotic diuretics (e.g. mannitol, urea) are inert compounds that are secreted into the proximal tubules of the kidney, and are not reabsorbed, so carry salts and water with them into the urine. Loop diuretics (e.g. ethacrynic acid, bumetanide, frusemide) have a vigorous action on the ascending tubules of the loop of Henle (inhibiting resorption of sodium and water, Read more […]

DIHYDROFOLATE REDUCTASE INHIBITORS have as a target the enzyme dihydrofolate reductase, and are known as folate antagonists. These include anticancer agents (‘antimetabolites’) such as methotrexate, antibacterial AGENTS such as trimethoprim, and the ANTIPROTOZOALS pyrimethamine and proguanil (which are used to treat malaria). Folate is required for synthesis of purine nucleotides, which in turn are essential for DNA synthesis and cell division. In mammals it is necessary to convert body folates, through two separate enzyme-catalysed reduction stages, to tetrahydrofolate (FH4). The first stage involves the enzyme dihydropteroate reductase, which catalyses the conversion of beta-aminobenzoic acid to folate (and this stage can be inhibited by sulphonamides). The second stage is conversion of folate to tetrahydrofolate by the enzyme dihydrofolate reductase. Methotrexate, trimethoprim, pyrimethamine and proguanil inhibit this latter conversion and lead to depletion of folic acid. Methotrexate is used as an oral anticancer agent, but resistance may develop in tumour cells, and there are a number of unwanted side-effects. It has a high affinity for the mammalian form of dihydrofolate reductase and cannot be used as an antibacterial Read more […]

DIGESTIVE AGENTS are taken to mean any of a variety of agents that aid in some way the digestive process. (See also NUTRITIONAL AGENTS.) Digestive enzymes may be given by mouth to make up deficiencies; e.g. chymotrypsin and pancreatin, which are currently used in human therapeutics to make up for deficiencies in secretions from the pancreatic exocrine gland (e.g. in cystic fibrosis and following pancreatectomy or chronic pancreatitis). They help digestion of starch, fat and protein. Cellulase was also once used, which is a concentrate of cellulose-splitting enzymes isolated from Aspergillus niger, and as a digestive adjunct. Papain, a purified proteolytic enzymic principle derived from Carica papaya, is essentially a vegetable pepsin. It is now not normally applied to food because of its adverse action on the gastrointestinal tract. ANTACIDS are used to neutralize gastric acid, by raising gastric pH, so inhibiting peptic enzyme activity, which is greatly inhibited above pH 5. Although antacids are used to give symptomatic relief of dyspepsia, oesophagitis and gastritis, there is little objective evidence of accelerated healing of peptic ulcers (gastric or duodenal). Examples of antacids include aluminium hydroxide, Read more […]

DERMATOLOGICAL AGENTS are used for a wide variety of purposes and some of the more important pharmacological types and terms will be discussed. ANTIINFLAMMATORY AGENTS are frequently used to treat inflammatory and/or allergic reactions of the skin. The commonest agents used are CORTICOSTEROIDS (of the GLUCOCORTICOID type), which have potent antiinflammatory and ANTIALLERGIC properties. There is a range of steroids available as creams or ointments, which vary in concentration and the strength of the antiinflammatory action of the particular corticosteroid: the choice depends on the severity of the skin condition. Some preparations are available without prescription for minor skin inflammation, whereas at the other extreme some preparations are reserved for severe outbursts of eczema or psoriasis. There are many corticosteroids used clinically for dermatological conditions. Inflammatory skin conditions are sometimes complicated by a coexisting infection, and there are many compound preparations available containing ANTIBACTERIAL or ANTIFUNGAL AGENTS together with an antiinflammatory corticosteroid. ANTIPERSPIRANTS are substances that help to prevent sweating. Medically, they are needed only in cases of severe Read more […]